#9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria : Free Download & Streaming : Internet Archive

Abstract

Plant-derived cannabinoids, including

#9-tetrahydrocannabinol (THC), induce apoptosis in

leukemic cells, althoughthe precise mechanism remains

unclear. In the current study, we investigated the effect

of THC on the upstream and downstream events that

modulate the extracellular signal-regulated kinase (ERK)

module of mitogen-activated protein kinase pathways

primarily in human Jurkat leukemia T cells. The

data showed that THC down-regulated Raf-1/mitogenactivated

protein kinase/ERK kinase (MEK)/ERK/RSK

pathwayleadingtotranslocationofBadtomitochondria.

THC also decreased the phosphorylation of Akt.

However, no significant association of Bad translocation

with phosphatidylinositol 3-kinase/Akt and protein

kinase A signaling pathways was noted when treated

cells were examined in relation to phosphorylation

status of Bad by Western blot and localization of Bad to

mitochondria by confocal analysis. Furthermore, THC

treatment decreased the Bad phosphorylation at Ser112

but failed to alter the level of phospho-Bad on site

Ser136 that has been reported to be associated with

phosphatidylinositol3-kinase/Aktsignalpathway.Jurkat

cells expressing a constitutively active MEK construct

were found to be resistant to THC-mediated apoptosis

and failed to exhibit decreased phospho-Bad on Ser112

as well as Bad translocation to mitochondria. Finally,

useofBad smallinterferingRNAreducedtheexpression

of Bad in Jurkat cells leading to increased resistance

to THC-mediated apoptosis. Together, these data

suggested that Raf-1/MEK/ERK/RSK-mediated Bad translocationplayedacriticalroleinTHC-inducedapoptosis

in Jurkat cells. (Mol Cancer Res 2006;4(8):549â62)

http://mcr.aacrjournals.org/content/4/8/549.full

Mediatype:	texts
Identifier:	9-tetrahydrocannabinol-inducedApoptosisInJurkatLeukemiaTCellsIs
Identifier-access:	http://www.archive.org/details/9-tetrahydrocannabinol-inducedApoptosisInJurkatLeukemiaTCellsIs
Identifier-ark:	ark:/13960/t4sj29d2c
Ppi:	300
Ocr:	ABBYY FineReader 8.0

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#9-Tetrahydrocannabinol-Induced Apoptosis in Jurkat Leukemia T Cells Is Regulated by Translocation of Bad to Mitochondria

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